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Diabetologia

Erschienen in:

01.05.2011 | Article

In vivo genetic engineering of murine pancreatic beta cells mediated by single-stranded adeno-associated viral vectors of serotypes 6, 8 and 9

verfasst von: V. Jimenez, E. Ayuso, C. Mallol, J. Agudo, A. Casellas, M. Obach, S. Muñoz, A. Salavert, F. Bosch

Erschienen in: Diabetologia | Ausgabe 5/2011

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Abstract

Aims/hypothesis

The genetic engineering of pancreatic beta cells could be a powerful tool for examining the role of key genes in the cause and treatment of diabetes. Here we performed a comparative study of the ability of single-stranded (ss) adeno-associated viral vectors (AAV) of serotypes 6, 8 and 9 to transduce the pancreas in vivo.

Methods

AAV6, AAV8 and AAV9 vectors encoding marker genes were delivered to the pancreas via intraductal or systemic administration. Transduced cells were analysed by immunostaining. AAV9 vectors encoding hepatocyte growth factor (HGF) were delivered intraductally to a transgenic mouse model of type 1 diabetes and glycaemia was monitored.

Results

AAV6, AAV8 and AAV9 mediated efficient and long-term transduction of beta cells, with AAV6 and AAV8 showing the highest efficiency. However, alpha cells were poorly transduced. Acinar cells were transduced by the three serotypes tested and ductal cells only by AAV6. In addition, intraductal delivery resulted in higher AAV-mediated transduction of the pancreas than did systemic administration. As proof of concept, intraductal delivery of AAV9 vectors encoding for the beta cell anti-apoptotic and mitogenic HGF preserved beta cell mass, diminished lymphocytic infiltration of the islets and protected mice from autoimmune diabetes.

Conclusions/interpretation

Intraductal administration of AAV6, AAV8 and AAV9 is an efficient way to genetically manipulate the pancreas in vivo. This technology may prove useful in the study of islet physiopathology and in assessment of new gene therapy approaches designed to regenerate beta cell mass during diabetes.

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Titel: In vivo genetic engineering of murine pancreatic beta cells mediated by single-stranded adeno-associated viral vectors of serotypes 6, 8 and 9
verfasst von: V. Jimenez
E. Ayuso
C. Mallol
J. Agudo
A. Casellas
M. Obach
S. Muñoz
A. Salavert
F. Bosch
Publikationsdatum: 01.05.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2070-3

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Abstract

Aims/hypothesis

Methods

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